title: Bottom-up signaling from HGF-containing surfaces promotes hepatic differentiation of mesenchymal stem cells.
abstract: The capacity of stem cells to differentiate into specific cell types makes them very promising in tissue regeneration and repair. However, realizing this promise requires novel methods for guiding lineage-specific differentiation of stem cells. In this study, hepatocyte growth factor (HGF), an important morphogen in liver development, was co-printed with collagen I (Col) to create arrays of protein spots on glass. Human adipose stem cells (ASCs) were cultured on top of the HGF/Col spots for 2weeks. The effects of surface-immobilized HGF on hepatic differentiation of ASCs were analyzed using RT-PCR, ELISA and immunocytochemistry. Stimulation of stem cells with HGF from the bottom-up caused an upregulation in synthesis of α-fetoprotein and albumin, as determined by immunocytochemistry and ELISA. RT-PCR results showed that the mRNA levels for albumin, α-fetoprotein and α1-antitrypsin were 10- to 20-fold higher in stem cells cultured on the HGF/Col arrays compared to stem cells on Col only spots. Our results show that surfaces containing HGF co-printed with ECM proteins may be used to differentiate mesenchymal stem cells such as ASCs into hepatocyte-like cells. These results underscore the utility of growth factor-containing culture surfaces for stem cell differentiation.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Mahboobe
authors.initials: M
authors.lastname: Ghaedi
authors.forename: Nazgul
authors.initials: N
authors.lastname: Tuleuova
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zern
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Alexander
authors.initials: A
authors.lastname: Revzin
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D019070:Cell Lineage; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D055767:Immobilized Proteins / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008115:Liver Regeneration; D059630:Mesenchymal Stem Cells / Q000187:drug effects*
chemical_list: D024042:Collagen Type I; D055767:Immobilized Proteins; D017228:Hepatocyte Growth Factor